A Study to Evaluate the Pharmacokinetics (PK) and Safety of a Single Dose of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Normal Hepatic Function and Participants With Hepatic Impairment

An Open-label, Phase 1 Trial to Evaluate the Pharmacokinetics and Safety of a Single Dose of 80 μg Treprostinil Palmitil Inhalation Powder in Participants With Normal Hepatic Function and Participants With Hepatic Impairment

The primary purpose of the study is to determine the effect of mild, moderate, and severe hepatic impairment on the PK of total treprostinil palmitil (TP) and treprostinil (TRE) following a single dose of 80 micrograms (μg) TPIP, when compared to normal hepatic function.

Study Overview

• Status: Not yet recruiting
• Conditions: Hepatic Impairment
• Intervention / Treatment: Drug: Treprostinil Palmitil Inhalation Powder

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Insmed Medical Information; Phone Number: 18444467633; Email: medicalinformation@insmed.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Body mass index between 18.0 and 40.0 kilograms per square meter (kg/m^2), inclusive.

Inclusion Criteria for Participants with Normal Hepatic Function

• In good health, as determined by no clinically significant findings from medical history, physical examination, 12-lead electrocardiogram (ECG), and vital signs measurements, and clinical laboratory assessments (congenital nonhemolytic hyperbilirubinemia [eg, suspicion of Gilbert's syndrome based on total and direct bilirubin] is not acceptable) at screening and check-in, as assessed by the investigator (or designee).

Inclusion Criteria for Participants With Hepatic Impairment:

• Diagnosis of chronic (>6 months), stable hepatic impairment with no clinically significant changes within 30 days prior to dosing, as determined by medical history.

• Participants with type 2 diabetes mellitus may be included, if they have:

  • glycosylated hemoglobin A1C ≤8.5% at screening
  • fasting blood glucose ≤240 milligrams per deciliter (mg/dL), while participant is using their normal diabetes medication, at screening and check-in.

Exclusion Criteria:

• History of stomach or intestinal surgery or resection that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair are allowed).
• Use or intend to use any moderate or strong inducers or inhibitors of CYP2C8 or CYP2C9 within 30 days prior to dosing.
• Participation in a clinical trial involving administration of an investigational medicinal product (IMP) (new chemical entity) in the past 30 days or 5 half-lives of that drug (if known) prior to dosing, whichever is longer.

Exclusion Criteria for Participants with Normal Hepatic Function

• Significant history or clinical manifestation of any metabolic, allergic, dermatological, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, neurological, respiratory, endocrine, or psychiatric disorder, as determined by the investigator (or designee).
• Positive hepatitis panel and/or positive human immunodeficiency virus test. Participants whose results are compatible with prior immunization may be included.
• Positive urine drug screen at screening or positive alcohol test result or positive urine drug screen at check-in. Results that are compatible with marijuana use are not exclusionary.

Exclusion Criteria for Participants With Hepatic Impairment:

• Current organ transplant or waiting for organ transplant scheduled to occur during the trial.
• Hospitalization for hepatic encephalopathy within 3 months prior to dosing.
• Encephalopathy ≥Grade 2.
• History of drug/chemical abuse within 1 year prior to check-in. Marijuana use is not exclusionary.

Note: Other protocol-defined inclusion/exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1: Treprostinil Palmitil Inhalation Powder; Healthy participants with normal hepatic function will receive a single dose of TPIP on Day 1.	Drug: Treprostinil Palmitil Inhalation Powder; Oral inhalation using a dry powder inhaler device.; Other Names: INS1009
Experimental: Group 2: Treprostinil Palmitil Inhalation Powder; Participants with mild hepatic impairment (classified based on the numerical Child-Pugh total score of 5 to 6) will receive a single dose of TPIP on Day 1.	Drug: Treprostinil Palmitil Inhalation Powder; Oral inhalation using a dry powder inhaler device.; Other Names: INS1009
Experimental: Group 3: Treprostinil Palmitil Inhalation Powder; Participants with moderate hepatic impairment (classified based on the numerical Child-Pugh total score of 7 to 9) will receive a single dose of TPIP on Day 1.	Drug: Treprostinil Palmitil Inhalation Powder; Oral inhalation using a dry powder inhaler device.; Other Names: INS1009
Experimental: Group 4: Treprostinil Palmitil Inhalation Powder; Participants with severe hepatic impairment (classified based on the numerical Child-Pugh total score of 10 to 15) will receive a single dose of TPIP on Day 1.	Drug: Treprostinil Palmitil Inhalation Powder; Oral inhalation using a dry powder inhaler device.; Other Names: INS1009

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area Under the Concentration-Time Curve From Time Zero to Infinity (AUCinf) of Treprostinil Palmitil (TP) and Treprostinil (TRE)	Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.	Pre-dose and at multiple timepoints post-dose up to Day 3
Area Under the Concentration-Time Curve From Time Zero to Last Quantifiable Concentration (AUClast) of TP and TRE	Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.	Pre-dose and at multiple timepoints post-dose up to Day 3
Maximum Observed Plasma Concentration (Cmax) of TP and TRE	Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.	Pre-dose and at multiple timepoints post-dose up to Day 3
Apparent Total Clearance (CL/F) of TP and TRE	Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.	Pre-dose and at multiple timepoints post-dose up to Day 3
Apparent Terminal Elimination Half-Life (t1/2) of TP and TRE	Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.	Pre-dose and at multiple timepoints post-dose up to Day 3
Time to Maximum Observed Concentration (Tmax) of TP and TRE	Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.	Pre-dose and at multiple timepoints post-dose up to Day 3
Apparent Volume of Distribution (Vz/F) of TP and TRE	Determination of the effect of mild, moderate, and severe hepatic impairment on the PK of TP and TRE following a single dose of TPIP, when compared to normal hepatic function.	Pre-dose and at multiple timepoints post-dose up to Day 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fraction Unbound (Fu) of TRE	Determination of the effect of mild, moderate, and severe hepatic impairment on the unbound PK of TRE following a single dose of TPIP, when compared to normal hepatic function.	Pre-dose and at multiple timepoints post-dose on Days 1 and 2
Number of Participants Who Experienced At Least One Adverse Event (AE)	Evaluation of safety and tolerability of a single dose of TPIP in participants with mild, moderate, and severe hepatic impairment and normal hepatic function.	Up to Day 7

Collaborators and Investigators

• Sponsor: Insmed Incorporated
• Investigators: Study Director: Study Director, Insmed Incorporated

Study record dates

Study Major Dates

• Study Start (Estimated): June 10, 2026
• Primary Completion (Estimated): February 7, 2027
• Study Completion (Estimated): February 7, 2027

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 11, 2026

Study Record Updates

• Last Update Posted (Actual): June 11, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: INS1009-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No